In vitro and in vivo effects of a cyclic peptide with affinity for the alpha v beta 3 integrin in human melanoma cells

Expression of the integrin alpha nu beta 3 has been shown to be associated with increasing metastatic potential in malignant melanoma. It also has a f unctional role on vascular endothelial cells during angiogenesis. The cycli c oligopeptide cRGDfV is known to bind with high affinity to alpha nu beta 3. We have investigated the cellular effects of cRGDfV on a panel of human melanoma cell lines in vitro and also on the A375 melanoma cell line growin g as xenografts in nude mice. cRGDfV is a potent inhibitor of alpha nu beta 3-mediated cell adhesion, however, we have found no convincing evidence th at integrin ligation by cRGDfV induces apoptosis in melanoma cell lines. Ho wever, cRGDfV when administered subcutaneously into nude mice did inhibit t he growth of A375 melanoma xenografts. Histological examination of the tumo urs indicated that this effect was primarily one of angiogenesis inhibition . The results suggest that agents which target the alpha nu beta 3 integrin may have a useful role as anti-angiogenesis agents in clinical oncology, b ut that they may not exert a direct effect on alpha nu beta 3-expressing tu mour cells. (C) 2000 Elsevier Science Ltd. All rights reserved.